The lung is a major dose-limiting organ to the delivery of adequate levels of irradiation to eradicate malignant disease. Lung tissue toxicity which manifests clinically as radiation pneumonitis is a serious and common complication. Recently the type II pneumocyte, the cell largely responsible for pulmonary surfactant production, has been demonstrated to be particularly radiosensitive, exhibiting loss of surfactant-containing lamellar bodies and increase in phosphatidylcholine secretion following irradiation (Penney and Rubin, 1977; Rubin et al., 1979). The goal of this project is to examine the role of the surfactant system in the development of radiation pneumonitis and to ascertain whether type II pneumocyte structural and/or functional alterations serve as predictive indices for latent adverse pulmonary changes. Three model systems will be employed to evaluate the effect of irradiation on the surfactant system: 1) A type II pneumocyte tumor cell line (A549); 2) cell cultures of isolated rabbit type II cells; and 3) intact mouse lungs. Experiments are designed to define radiation dosages which effect sublethal and lethal responses both in vitro and in vivo and both with and without drugs. Specific cellular responses of type II pneumocytes to radiation insult will be determined with particular emphasis on those early responses of type II cells which correlate with lethality. Biochemical (enzyme assays, uptake of surfactant precursors, and phosphatidylcholine synthesis and secretion), morphological (light and electron microscopy, enzyme localization, stereology, and light and electron autoradiography) and pathophysiological (lethality) parameters will be correlated in a multifaceted approach to identify early (less than 1 week) post-irradiation changes which may be predictive for later pulmonary change.